Novel mutations in the LKB1/STK11 gene in Dutch Peutz-Jeghers families

Abstract

The Peutz-Jeghers syndrome (PJS) is a rare hereditary disorder in which gastrointestinal hamartomatous polyposis, mucocutaneous pigmentation, and a predisposition for developing cancer are transmitted in an autosomal dominant fashion. The recently identified LKB1/STK11 gene located at chromosome 19p13.3 is mutated in a number of PJS pedigrees. We performed mutation analysis in 19, predominantly Dutch, PJS families. In 12 of these families, we identified LKB1/STK11 mutations, none of which has been described before. These 12 novel LKB1/STK11 mutations consist of one nonsense mutation, three frameshift deletions, three frameshift insertions, two acceptor splice site mutations, and three missense mutations. In addition, we detected four polymorphisms in LKB1/STK11. In the remaining seven PJS families, we found no apparent abnormalities of the LKB1/STK1I gene, which could reflect the existence of locus heterogeneity in PJS. None of the mutations occurred in more than one family, and a number were demonstrated to have arisen de novo. The diverse array of mutations found, the apparent high mutation rate, as well as the existence of a possible second PJS locus, renders diagnostic or predictive genetic testing in individual patients difficult, although future identification of additional mutations or even gene(s) will help in increasing the yield of direct mutation analysis.

A novel mutation of STK11/LKB1 gene leads to the loss of cell growth inhibition in head and neck squamous cell carcinoma

“…The exon 1 ATC88ATA and exon 6 TAC272TAT are previously described SNPs (Sanchez-Cespedes et al, 2002), whereas exon 2 CAG123CAA is a novel SNP. Five of the seven intronic polymorphic variants observed in the study, occurring in the intron 1 ( þ 36 G-T), intron 2 ( þ 24 G-C, À49 G-A), intron 3 (À51 T-C) and intron 7 ( þ 7 G-C), have been reported previously Rowan et al, 1999;Su et al, 1999;Westerman et al, 1999). The other two polymorphic changes in the intron 1 (À32 C-T) and intron 4 (À16 C-G) are not noted in the previous studies (Table 2).…”

Molecular and Clinical Characteristics in 46 Families Affected with Peutz–Jeghers Syndrome

“…There is no evidence that these 2 mutations have a common ancestry [17]. Similar situations have been reported by others [10,[18][19][20]. In 11 of 17 apparently sporadic cases, the DNA from both parents of the affected individuals did not have these mutations and the possibility of nonpaternity or nonmaternity was excluded using microsatellite markers.…”

Correlation of Staining for LKB1 and COX-2 in Hamartomatous Polyps and Carcinomas from Patients with Peutz–Jeghers Syndrome

“…This heterogeneity may be due to differences in somatic alteration in the PJPs in these patients. Previous studies suggest genetic heterogeneity in PJS (Mehenni et al 1997;Olschwang et al 1998;Westerman et al 1999; body. LKB1 and COX-2 were detected with DAB (brown) and nuclei were counterstained with hematoxylin.…”